Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

Locally Advanced Pancreatic Adenocarcinoma Clinical Trial

Official title:

Phase IIa Trial Evaluating the Safety of Intratumoral Injection of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03077685
• Other study ID #: NANOPAC-2016-05
• Status: Completed
• Phase: Phase 2
• Start date: December 1, 2017
• Est. completion date: March 15, 2023

Study information

• Verified date: November 2023
• Source: NanOlogy, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, dose-escalating, Phase IIa trial of NanoPac® to treat subjects with locally advanced pancreatic adenocarcinoma via direct intratumoral injection.

Description:

In this open-label, dose-escalating, Phase IIa trial, subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection. Subjects will be enrolled in sequential cohorts of NanoPac® at escalating doses, at a volume based on up to 20% of calculated tumor volume (with a maximum injection volume of 5 mL per subject). Each cohort will have three subjects, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data, the next cohort may begin enrolling, an additional three subjects at the current dose may be enrolled, or if the first dose does not provide adequate safety and tolerability the study may be halted. The dose determined to be most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile as determined by the Data Safety Monitoring Board (DSMB), will be the dose used in the second phase of the study which will enroll 22 additional subjects who will receive two injections of NanoPac® at the same dose one month apart. In the third phase of the study, up to 30 subjects will receive up to four injections of NanoPac at the same dose, one month apart. Plasma samples will be taken at various time points on the day of NanoPac® injection as well as once at each of the study visits, to characterize the pharmacokinetics (PK) of intratumoral NanoPac®. Subjects will be followed for 12 months after NanoPac® injection for safety, overall survival (OS), progression-free survival (PFS), CA-19-9 levels, carcinoembryonic antigen (CEA) levels, reduction in pain, and tumor response to therapy (as shown by imaging).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: March 15, 2023
• Est. primary completion date: March 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent;
• Age =18 years;
• Histologically/cytologically confirmed locally advanced pancreatic adenocarcinoma; at least one lesion with a diameter of at least 1.5 cm but no more than 6 cm as documented via imaging (within 6 weeks of Screening);
• Subject not a candidate for surgery;
• Completion of at least one standard of care IV chemotherapy course for subjects in the dose escalation phase of the study. IV chemotherapy will be initiated prior to first NanoPac injection for subjects in the second and third phases. Hematologic recovery must be confirmed prior to study entry;
• Performance Status (ECOG) 0-1 at study entry;
• Life expectancy of at least 3 months;
• Adequate marrow, liver, and renal function at study entry:
• ANC = 1.5 x 109/L
• Hemoglobin = 9.5 grams/dL
• Platelets = 75 x 109/L
• Total bilirubin = 1.5x institutional ULN
• AST/ ALT = 2.5x institutional ULN
• Creatinine = 1.5x institutional ULN
• Effective contraception if the risk of conception exists.

Exclusion Criteria:

• Thrombotic or embolic events;
• Acute or subacute intestinal occlusion;
• History of inflammatory bowel disease;
• Known hypersensitivity to study drugs;
• Known drug or alcohol abuse;
• Pregnant or breastfeeding women;
• Previous or concurrent history of non-pancreatic malignancy except for non-melanoma skin cancer.

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Pancreatic Adenocarcinoma

Intervention

Drug:
• NanoPac®
Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.

Locations

Country	Name	City	State
United States	Texas Tech University Health Sciences Center	El Paso	Texas
United States	Parkview Cancer Institute	Fort Wayne	Indiana
United States	Baylor College of Medicine	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
NanOlogy, LLC	US Biotest, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (4)

ABRAXANE Package Insert. Celgene Company. Rev July 2015.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. — View Citation

Taxol® (paclitaxel) Injection Package Insert. Bristol-Myers Squibb Company. Rev July 2011.

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events (safety and tolerability)	Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs.	Up to 6 (six) months after NanoPac® injection
Secondary	Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of NanoPac®	Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 6, and 24 hours post-injection, and again at all study visits post-injection	Up to 6 (six) months after NanoPac® injection
Secondary	Pharmacokinetics: Peak plasma concentration (Cmax) of NanoPac®	Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 6, and 24 hours post-injection, and again at all study visits post-injection	Up to 6 (six) months after NanoPac® injection
Secondary	Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of NanoPac®	Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 6, and 24 hours post-injection, and again at all study visits post-injection	Up to 6 (six) months after NanoPac® injection
Secondary	Tumor Response (RECIST)	Tumor burden at 3 months after NanoPac® injection will be compared with baseline tumor burden.	Baseline and every 3 (three) months after NanoPac® injection, up to 12 months
Secondary	Change in pain score	Pain scores will be measured using a visual analog scale	Baseline and 3 (three) months after NanoPac® injection
Secondary	Change in tumor markers	Tumor markers measured will include CEA and CA19-9	Baseline, 3 (three) months, and 6 (six) months after NanoPac® injection